Oxitocin: A double edged hormone?

by Kenta Hasui

Locked. Photograph by SMN

“Be nice.” “Stop being such a jerk!” “I just want to help . . . ”

Many of us have these phrases heard throughout our lives, whether from our parents, teachers, friends, T.V. shows or movies. Being nice has become a given, something obvious that everybody should strive towards. But throughout this past century the discovery of the hormone oxytocin has changed how scientists and psychologists think about terms such as nice, mean, helpful, loving or altruistic.

First discovered in 1909 by scientist Sir Henry Dale, oxytocin is a hormone produced in the hypothalamus and passed through the posterior pituitary gland into the bloodstream. (Lee, Macbeth, Pagani & Young, 2009). Dale noticed that injecting an extract of oxytocin from a human into a pregnant cat contracted the cat’s uterus. He thus named the substance oxytocin, after the Greek words “quick” and “birth.” For years, oxytocin was thought primarily as a hormone for mothers during or right after childbirth.

However, the oxytocin receptors that were found in a pregnant woman’s uterus were also found in other tissues, regardless of the person’s sex. These receptor sites ranged from the heart, brain, and reproductive tract. Thus recent research have focused on the effects of oxytocin on the brain and social behavior. One such study, led by researchers from Concordia University (2011), was a randomized double-blind study on 100 university students gauging the effects of an oxytocin nasal spray . Half of the subjects inhaled oxytocin from a nasal spray while the other half received a placebo. They then completed questionnaires on their personality after 90 minutes, testing for extraversion, agreeableness, conscientiousness and neuroticism.

The subjects who received the nasal spray had higher ratings of extraversion, positive emotions, warmth, openness to ideas, trust and altruism. The researchers believed that people’s self-perception of these personality traits were important for navigating social situations. Thus the researchers concluded that this positive self-perception could lead to an increase in positive social behaviors.

Other studies have presented similar results for the relationship between oxytocin and trust in humans. Fehr (2005) demonstrated that oxytocin affects how willing a person is to accept risks through  interactions with other people. It does not lead people to take more risks regardless of the situation – they must be social risks  (DeAngelis, 2008). Similarly, a study from the University of Buffalo (2012) concluded that people with certain versions of oxytocin receptor genes were more likely to be generous and sociable (University at Buffalo, 2012).

However, it’s important to keep in mind that oxytocin is not a perfect hormone for niceness. Although oxytocin promotes trust in one’s in-group, it promotes distrust in one’s out-group , or the people seen as different. De Dreu (2010) illustrated that doses of oxytocin made people much more likely to help an ethnic in-group at the expense of the out-group  In one experiment, Dutch students were given moral dilemmas in which a choice must be made about whether to help a person onto an overloaded lifeboat and drown the five on it, or save five people in front of a train by throwing a bystander onto the tracks. The five people who were to be saved had no name, but the sacrificial victim had either a Dutch or a Muslim name. These two nationalities were chosen because of a poll in 2005 illustrating that 51% of Dutch citizens held unfavorable opinions about Muslims. Thus the Dutch were the in group and the Muslims were the out group. Subjects who had who had sniffed a dose of oxytocin were far more likely to sacrifice the Muhammads than the Maartens (De Dreu, 2010). In another experiment, De Dreu asked participants to press a key when shown a pair of words. One word had either a positive or negative connotation, and the other was a common Dutch first name such as Peter, or an out-group name such as Ahmad to represent Muslims.

Sinister, or even-minded?

By Heather Kobayashi

Photo by Jeff the Trojan

There’s more to being a lefty than just which hand you write with.  That sentence may sound wrong to some, but a growing body of research shows a many unexpected differences between different-handed individuals.

In everyday speech, there is seeming equivalence between “right” as opposed to wrong and “right” as opposed to left; however, there are some advantages to being “sinister,” or “gauche,” both originally words for left which have become pejorative in modern language.  Left-handers have had disproportionate representation in the White House: including President Obama, 18.6% of US Presidents (8/43) have been left-handed, approximately double the percentage in the general population.  Recent research also suggests that left-handers have a more accurate body sense than right-handers: when asked to estimate arm length, left-handed people estimated both arms as being the same length, while right-handed people tended to underestimate the length of their left arms.  Similarly, left-handed people estimate that both of their hands are the same size, whereas right-handed people estimate that their right hand is larger.    Researchers theorize that this difference indicates a variance in neural networks, the physical pathways of the brain, with right handed people devoting more brain matter to mapping of the right side of their bodies.  Left-handed people, instead of having a larger brain map of their left sides, devote neural space about equally to both halves of their bodies–a decidedly less lop-sided approach.  In fact, lateralization, as distribution of functions between the hemispheres is called, has garnered attention particularly where handedness is concerned.

Brain lateralization may relate to some of the disadvantages of being a lefty.  Geschwind and Behen (1984) found a correlation between left-handedness and a host of immune and respiratory disorders as well as some learning and language disorders. They theorized that the diseases and disorders, brain lateralization, and handedness itself are all due to higher pre-natal testosterone exposure; however, they were also quick to speculate that there are some disorders which have lower occurrence rates among “sinistrals” and cited the higher than average rate of left-handedness in highly skilled professions such as architecture as evidence that left-handed people are not overall less intelligent or healthy.  More recent research has cast some doubt on this theory, asserting that the hypothesis itself is ill-defined (Bryden, McManus, and Bulman Fleming, 1994).  Geschwind and Behan failed to specify what levels of handedness and lateralization were supposed to correlate on the continuums of both scales and a meta-analysis of psychological research shows no particular support of the 1984 findings.  Nevertheless, they still remain heavily cited because no stronger model of handedness has emerged. In addition, studies do show that lefties live, on average, 3 fewer years than their dexterous colleagues (Myers, 2007).  This phenomenon may have its roots in–rather than a psychological difference–the greater number of workplace accidents that befall left-handed people because of mechanical systems designed for righties (a more severe form of the “there are no left-handed scissors” phenomenon in my kindergarten classroom).  Identical twins often have different handedness, so some factor besides genetics must be in effect, but there is also high heritability of the trait (Myers, 2007).  Thus, it remains unclear exactly how handedness, health, and the brain are related.

The evolution of ADHD

by Eric Schuman

Photo by by Ptit@l

Research has shown that ADHD (Attention deficit / hyperactivity disorder)  is strongly influenced by genes. It seems as if it is related to a problem within the dopamine reward system of the brain. Difficulties with this system could be the  reason that people with ADHD and ADD (attention deficit disorder) seem to have trouble staying focused.

The bad side of  ADHD is pretty obvious: It makes people seem unfocused, hyperactive. But new research proposes that it has benefits. Why else would the genes associated with ADHD still be in the gene pool?  Researchers Dan Eisenberg of Northwestern University and Ben Campbell of the University of Wisconson, Milwakee, think they have an answer. In a study published in BMC Evolutionary Biology, they posit that the sort of activities associated with ADHD—a want of novelty, behavioral flexibility, being hyper-aware in environments—were in fact advantageous to nomadic herdsman. They  go on to link ADHD to obesity. In the modern world where a scarcity of food (for many but clearly not all) no longer exists, dis-inhibition of seeking pleasure from things like food become exaggerated, leading to obesity. Many  children with ADHD have higher BMI’s (body mass index) than their peers, before they go on  medications that often lead to weight loss, they point out.

Campbell, Eisenberg and their collegues (2008) studied a tribe in Kenya. One half had stayed nomadic, and the other had become agricultural. They  explain that within a nomadic context, the ADHD genes are beneficiary. When in a more sedentary context, those same genes result in increased weight and malnutrition. This allele that contains these genes is, of course, connected with ADHD. Therefore, it seems ADHD is both positive and negative.

Newly discovered mutations tied to schizophrenia

by Stacy Locke

Psychologists have long been trying to unravel the mystery of schizophrenia. A recent study has found rare genetic variations in Schizophrenic patients that were previously undetected, which could point us in the right direction to understanding why and how a person develops schizophrenia.
The New York Times Science section reveals the new analysis, originally published in the journal Science. The researchers detected rare and unknown genetic mutations that occur three to four times more often in Schizophrenics than others. This collaboration involved the National Institute of Mental Health, The University of Washington, Seattle, and Cold Spring Harbor Laboratory. Blood samples were analyzed from 150 Schizophrenics and 268 people with no psychiatric disorders, using a new high-resolution technique. 53 of these mutations were found overall, showing not only a tendency in Schizophrenics, but also in a specific sub-group that developed the disorder in childhood. This discovery could point to an even more complex underlying genetic reason for the disorder than was previously believed.
This new study could indicate a new direction in Schizophrenia research, but even the senior author Jonathan Sebat admits that there is a long way to go and the findings could mean very little in the grand scheme of things. The most important thing to be taken from this study is that it provides evidence that the new high-resolution scanning technique can be successfully used to find minor genetic variations. “The take-home message is that there’s a new way to search for genetic links, and this new method goes straight to the underlying biology,” stated Sebat. This means it could help with understanding many disorders, not just schizophrenia.

Reference:

Carey, B. (2006, March 25). Study Ties Genetic Variations to Schizophrenia. New York Times.

http://www.nytimes.com/2008/03/28/science/28gene.html?_r=1&oref=slogin

A Valentine’s Day Mystery

by Stacy Locke

Love is one of the greatest mysteries of life: How does one individual become attracted to another? And furthermore, can the potential for, and longevity of, a relationship be predicted?

The February 2008 issue of Psychology Today lends some new insight into love within the article “Scents and Sensibility.” The article describes new research that connects attraction and compatibility with scent. A biologist at the University of Lausanna in Switzerland, Claus Wedekind, conducted a study that lends great evidence to this theory. 44 men were given new, clean t-shirts and asked to wear them for two nights straight without using any extraneous, artificial scents. 49 women sniffed the shirts and specified which odors they found most attractive. Results showed a strong tendency for women to prefer the scents of men who were “immunologically dissimilar to them,” that is, men who differ in their genetic code in terms of MHC or major histocompatibility complex, which helps the immune system recognize pathogens. This would serve a biological purpose in that it creates couples that will produce more disease-resistant children.

Interestingly enough, however, a similar study conducted by Martha McClintock found that women were not attracted to the scent of men who had none of the same MHC genes as them. This suggests that there is a critical balance point between too much in common and too much difference. Geneticist Carl Ober found that couples with high MHC similarity had more trouble conceiving. Furthermore, Psychologist Christine Garver-Apgar found a correlation between high MHC similarity and a high likelihood of cheating.

Could these findings prove once and for all the existence of “sexual chemistry?” Should we all go without perfumes and scented products so as to not distract from our natural scent? Perhaps love can be explained in a psychological context much more easily than we ever thought.

Reference:

Svoboda, E. (2008). Scents and Sensibility. Psychology Today. 41(1), 66-73.

Handedness, hair whorls, and homosexuality

by Nicholas Katz

Handedness is an attribute of human beings defined by their unequal distribution of fine motor skill between the left and right hands. An individual who is more dexterous with the right hand is called right-handed (RH); all others are called non-right-handers (NRH) when studied scientifically. About 91% of the population are right-handers, the rest are non-right-handers. Most people assume that there is no single ‘handedness’ gene because it is not simply inherited. Two left-handed parents, for example, will often have right-handed children. Dr. Amar Klar, a researcher at the National Cancer Institute came up with a new theory that seems to explain how this is possible. The basics of which are described here.

Suppose there is a single gene that controls handedness, called RGHT. If you have a RR or Rr, you are RH. If being a NRH is a recessive gene, then all NRH would have to be rr. Thus, all the children of two NRH would have to be NRH. Klar explains this by suggesting what he calls a “random recessive” gene. This means that those who have the rr gene have a 50% chance of being either RH or NRH. Thus of the population, the 91% RH are either RR, Rr, or rr, and the 9% NRH are all rr. More on the genetics can be found here. Klar also related this to hair whorls, which is the direction the hair on the top of your head spins. 91% of the population had clockwise hair whorls, while 9% have counter clockwise hair whorls. Thus, the majority of the population is right handed and has a clockwise hair whorls. Those who are NRH have a 50/50 shot of having a clockwise or counterclockwise whorl. This led Klar to hypothesize that the genetics of hair whorls and handedness are related. Klar’s full article can be found here. Klar also investigated the link between homosexuality and hair whorls, and found that homosexual men have increased rates of counterclockwise hair whorls. This study can be found here.

Do-gooder genes?

by Kenia Rodriguez

As a native New Yorker I am used to watching dozens of people walk right past donation tables or street beggars without even a second thought. I’m actually surprised when people do take the time to stop and give a quarter or a nickel. But what it is about these particular individuals that makes them more likely to give money to others?

Dr. Ariel Knafo of the Psychology Department at the Hebrew University of Jerusalem and his team have been wondering just that. In a recent study, subjects were to play an online game and in which they would be awarded $12 for their win. The players could either choose to keep the money or give part or all of it to an anonymous other player. Samples of DNA from each subject were also taken prior to the experiment.

The results of the experiment were quite surprising. Those subjects who had variants of a gene called AVPR1a gave, on average, about 50 percent more money than those who did not display the gene variant. The gene AVPR1a codes for the activation of the hormone Vasopressin which is responsible for social bonding. This means that a relationship exists between genetics and human altruism.

But how quick are we to believe that human generosity is owed to genetics? The results of this experiment bring about an interesting clash between the social teachings on morality versus the biological attributes of behavior. If our generosity is genetically based and has therefore served some evolutionary purpose (possibly to encourage cooperation between social groups to improve changes of survival), then why does it appear that generosity is so hard to find?

Will America become Forever Young?

by Sophia Alexandrov

For years, people have been turning to botox, facelifts, and plastic surgery in an attempt to eliminate wrinkles. While some of these methods may change physical appearances, they have no affect on the inner workings of the human being, and are unsuccessful in postponing the inevitable: the natural deterioration of their systems that we call “aging”.

Unlike some cultures that think of people as growing more beautiful with age, the trend with adults in the United States seems to be to stay as young as you can, for as long as you can. David Sinclair of Harvard Medical School and his company, Sitris Pharmaceuticals, are working on developing a drug that would produce that affect.

The goal of this project is to design a pill that triggers the body’s natural anti-aging processes, a group of enzymes called “sirtuins”, which are controlled by the genes SIRT1, SIRT2, SIRT3, and SIRT4. Research already shows that stimulation of SIRT1 helps yeast cells live longer, but it is not clear if the stimulation of the SIRT gene would have the same affect on humans.

The enzymes for SIRT3 and SIRT4 genes are responsible for making proteins that go into mitochondria , which are organelles found in most eukaryotic cells that generate Adenosine Triphosphate (ATP). ATP is used as an important source of energy. According to the Britannica Online Encyclopedia ATP obtains chemical energy from the breakdown of food molecules and releases it to fuel other cellular processes, such as initiating metabolic reactions that do not occur automatically, transporting substances across membranes, and performing mechanical processes such as muscle movement.

SIRT3 and SIRT4 are activated by elevated levels of a protein called NAD, which is important for carrying electrons, participating in metabolic redox reactions, and sending cell signals.

Sinclair and his team believe that if they can create a pill that will increase levels of NAD, SIRT3, and SIRT4 directly in the motochondria, there would be the possibility of slowing down the body’s natural aging processes and battling age related diseases such as heart disease, cancer, osteoporosis, and cataracts. Sitris Pharmaceuticals has already created an experimental pill called SRT501, which is currently being tested on patients with type-2 diabetes.

If a pill such as this were successfully created and utilized, it would have a drastic affect on humans, who would be able to live longer and healthier lives. But how would the use of this pill be regulated? Would people have the option of beginning to use the pill as soon as they began to show signs of aging, or would people only use it after they had been diagnosed with the age-related diseases? Would the pill work on all people, or would side effects of the pill make it only suitable for some?

All of these are questions that will inevitably be answered with time, which is something that all of us might have more of, if this new drug really can work miracles and extend the human life.

Sick and Lonely, a perfect match?

by Sean Boley

A group of scientists at the University of California Los Angeles and
the University of Chicago has recently set out to determine the what
causes the correlation chronically lonely individuals and a high rates
of sickness and death (“Sick? Lonely? Genes tell the tale.”). There are two theories
attempting to explain the reported (House, J. S., Landis, K. R. &
Umberson, D. (1988). Social relationships and health. /Science, /241,
540-545.) correlation between lonely people and rates of sickness. Some
scientists argue that the higher rates are due to a lack of friends and
neighbors to urge the lonely person to see a doctor. Others, the
scientists in the aforementioned study included, think that there is
something intrinsically different in the bodies of lonely people.

By studying the genome of very lonely individuals (volunteers who said
they have not felt close to someone for four years), the researchers
found that a certain subset (about 200) of the 22,000 human genes varied
in this population from normal people. It turned out that many genes in
this subset regulate immune system function, such as the response to
tissue damage and antibody production.

The question that arises is the age old, ‘which came first’ dilemma. Did
the chronic loneliness of the participants lead to a change in the genes
for immunity, or did the lack of certain immune functions cause a change
in the social behavior of the individual. This change in social behavior
could be the cause of either an internal aversion to social contact, or
an aversion by other people to contact the chronically sick person. This
could be a great example of adaptive evolution, as it would be
evolutionarily advantageous to stay away from people who always are
catching infections diseases.

I am of the opinion that any one of these explanations could be playing
a role in the observed correlation. Most likely, they are all playing a
minor role. This certainly presents itself as a promising area of
gene-behavior research. For example, one could study individuals who
have already have depressed immune systems, and observe their level of
loneliness. Alternatively, one could also study the behavior of normal
individuals toward individuals who are chronically sick.

Anecdotally, when I am sick, I don’t really feel like going out and
making friends. Could the explanation to this complex gene-behavior
relationship be as simple as that?

What if Monk were a mouse?

My favorite obsessive compulsive detective, Monk, may never clear up the mystery of who killed his beloved wife, but scientists are closer to clearing up the mystery of why Monk is obsessive compulsive. The new discovery is that mice who are missing a protein called SAPAP3 act like they, too, have OCD (obsessive compulsive disorder). They do not boil their toothbrushes before using them or wash their hands 100 times, of course, but then the compulsive behaviors of humans vary quite a bit from individual to individual anyway. Just like humans, these OCD mice exhibit what looks like an unhealthy obsession with cleanliness. They lick and groom themselves to the point of destroying their fur, and damaging their skin. They do this even when they should be sleeping. They do not solve mysteries, so far as we know.

How is it that these mice were missing that particular protein? Well, these are very special mice. They have been genetically engineered. Specifically, the gene that codes for SAPAP3 has been removed, or “knocked-out” of their DNA. We can call them SAPAP3 knock-out mice. And they were created for that best of scientific reasons: the researchers just wanted to see what would happen if you took that gene out.

This story should raise a lot of questions in the minds of readers who do not have a lot of background in genes and behavior.

Q: What does knocking out a gene affect a particular protein?

A: We think of genes as just being a kind of code, that passes on information about traits from parents to children. But in fact, genes are much more than that. They are protein factories. What you inherited from your parents are 23,299 little protein-building machines. It is the proteins they build that do the work of every cell in your body. Different kinds of cells get different proteins, because different genes are switched on and off for different cells. So these SAPAP3 knock-out mice have had the genes for that one protein effectively turned off for every cell.

Q: Why does a protein affect grooming behavior?

A: Like any behavior, grooming involves a great many neurons (nerve cells). Neurons “talk” to each other by means of chemicals called neurotransmitters. One neuron releases a neurotransmitter, and the next one picks it up. SAPAP3 plays a role in the transmission of the neurotransmitter glutamate. What brain circuitry is being messed up by the lack of SAPAP3 is not clear. Since glutamate is an excitatory neurotransmitter used all over the nervous system, there are many possibilities. So we know that the lack of SAPAP3 is interfering with the normal function of the nervous system, but we do not know exactly what it does to increase grooming.

I should also point out that the neurotransmitter more often associated with OCD and other anxiety related disorders is serotonin.

Q: Is there anything that can be done for these poor mice?

A: Yes! As it turns out, they respond to fluoxetine (prozac). This drug, which is also used to treat OCD in humans, significantly reduced their grooming behavior. This drug is a serotonin specific reuptake inhibitor (SSRI),  which only makes the glutamate connection more puzzling.

Q: Is Adrian Monk an SAPAP3 knock-out human?

A: Not in the same way as the mice. He has not been genetically engineered. But it is possible that natural genetic variations among humans contribute to OCD. It is also possible that lower production of this protein is involved in OCD in humans, but we will need new studies to look at this.

Something to keep in mind whenever you read a story about a gene that has been identified with this or that disorder: Just because the gene plays a role in some individuals does not mean that the same gene plays the same role in everyone. There might be multiple genes involved. There might be many pathways to the same illness. In fact, it is an entirely different gene linked to OCD that most researchers have been focused on the past several years.

One thing is clearly different between mice and men (at least OCD mice and men): For these mice this is purely genetic. In humans, it may be a mix of genes and experience. In some humans, that experience may be a strep throat, which then triggers an autoimmune response. Family dynamics and life stress certainly play a role in the ups and downs of OCD, but probably not in creating it.

Finally, it is worth pointing out that the mice’s behavior might not really be analogous to OCD in humans. OCD is one kind of anxiety disorder, but not the only kind. Self-grooming is a way to calm anxiety. Then again, so is touching every parking meter on the sidewalk as you go by, if you are Adrian Monk.